Dendritic cells and autoimmunity

Dendritic cells (DC) are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Because of their capacity to stimulate naive T cells, DC have a central role in the initiation of primary immune responses and are considered promising tools and targets for immunotherapy. Emerging data suggest a role for DC in initiating autoimmune attacks. Direct analysis of DC phenotypes and DC-T-cell interactions in rodent and human autoimmune diseases should shed light on how pathogenesis occurs, and suggest novel avenues of treatment aimed at alleviating deviant DC function.     

Learning increases stimulus salience in anterior inferior temporal cortex of the macaque.

With experience, an object can become behaviorally relevant and thereby quickly attract our interest when presented in a visual scene. A likely site of these learning effects is anterior inferior temporal (aIT) cortex, where neurons are thought to participate in the filtering of irrelevant information out of complex visual displays. We trained monkeys to saccade consistently to one of two pictures in an array, in return for a reward. The array was constructed by pairing two stimuli, one of which elicited a good response from the cell when presented alone ("good" stimulus) and the other of which elicited a poor response ("poor" stimulus). The activity of aIT cells was recorded while monkeys learned to saccade to either the good or poor stimulus in the array. We found that neuronal responses to the array were greater (before the saccade occurred) when training reinforced a saccade to the good stimulus than when training reinforced a saccade to the poor stimulus. This difference was not present on incorrect trials, i.e., when saccades to the incorrect stimulus were made. Thus the difference in activity was correlated with performance. The response difference grew over the course of the recording session, in parallel with the improvement in performance. The response difference was not preceded by a difference in the baseline activity of the cells, unlike what was found in studies of cued visual search and working memory in aIT cortex. Furthermore, we found similar effects in a version of the task in which any of 10 possible pairs of stimuli, prelearned before the recording session, could appear on a given trial, thereby precluding a working memory strategy. The results suggest that increasing the behavioral significance of a stimulus through training alters the neural representation of that stimulus in aIT cortex. As a result, neurons responding to features of the relevant stimulus may suppress neurons responding to features of irrelevant stimuli.     

Emergence of a nephropathogenic avian infectious bronchitis virus with a novel genotype in India

We describe the emergence of a nephropathogenic avian infectious bronchitis virus (IBV) with a novel genotype in India. The Indian IBV isolate exhibited a relatively high degree of sequence divergence with reference strains. The highest homology was observed with strain 6/82 (68%) and the least homology with strain Mex/1765/99 (34.3%).     

Safety & efficacy of single subconjunctival triamcinolone 5 mg depot vs topical loteprednol post cataract surgery: less drop cataract surgery

AIM: To do a randomized prospective interventional study for comparing the effects of a single subconjunctival triamcinolone acetonide (SCTA) injection to tapering topical loteprednol in patients undergoing phacoemulsification surgery under topical anesthesia. METHODS: A total of 400 patients were randomized into 2 groups; Group A (200 patients) received 5 mg SCTA at the end of surgery and topical ketorolac tromethamine (0.5%) with ofloxacin (0.3%) combination for 3wk. Group B (200 patients) received tapering topical loteprednol etabonate (0.5%) along with ofloxacin (0.3%) and ketorolac tromethamine (0.5%) for 3wk. Outcomes evaluated were intraocular pressure (IOP), anterior chamber cells/flare and macular oedema postoperatively at 1, 6 and 12wk. RESULTS: Baseline parameters were almost similar in both the groups. No statistical difference was seen between the preoperative and postoperative IOP values for Group A (P=0.82) and Group B (P=0.61) and postoperative IOP values in between both groups (P=0.14) at 1wk. Incidence of cells/flare postoperative was statistically not significant (P=0.82) in both groups at all follow up visits. Postoperative macular oedema was not observed at any follow up visit. CONCLUSION: SCTA appears to be an effective alternative to prolong postoperative topical steroid use.     

TREATMENT OF SUPERIOR VENA CAVA SYNDROME WITH RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR IN A SICKLE CELL PATIENT UNDERGOING BONE MARROW TRANSPLANTATION

Superior vena cava (SVC) syndrome is a well-recognized clinical entity seen with mediastinal malignancies and intraluminal venous thrombosis. The role of recombinant tissue plasminogen activator (rt-PA) in the resolution of SVC syndrome caused by thrombosis in the bone marrow transplant settings has not been described. The authors report a case of SVC syndrome with good clinical response in a 16-year-old female with sickle cell disease undergoing an allogeneic bone marrow transplant (BMT) from her HLA identical sibling. Shortly after her transplant, she was found to have significant facial edema and swelling above the neck. Concomitantly, her renal function deteriorated with progressive elevation of serum urea nitrogen and creatinine levels, requiring the use of continuous veno-venous hemofiltration. An upper extremity venogram showed complete SVC obstruction (type III) with apparent inferior reflux into the azygos system. rt-PA was started at a dose of (0.5 mg/kg/day) for 2 days. There was a dramatic resolution of her symptoms, including significant improvement in renal function with increase in urine output. A repeat venogram showed free flow from the distal tip of the central line consistent with a patent superior vena cava. There was no evidence of any bleeding manifestations with rt-PA. This report highlights the usefulness of rt-PA as a treatment modality for SVC syndrome in the BMT settings.     

Poly-Ingredient Formulation Bresol? Ameliorates Experimental Chronic Obstructive Pulmonary Disease (COPD) in Rats

In the present study, the protective effect of Bresol^® – a polyherbal formulation – was evaluated in an experimental model of cigarette smoke (CS)-induced COPD in rats. Ten minutes daily exposure to CS for 7 weeks caused significant elevation of TNF-α (p<0.01) and total protein (p<0.01) in the bronchoalveolar lavage fluid (BALF) of positive untreated control animals, indicating ongoing inflammatory process in the lungs. Further, histopathological findings have confirmed the presence of pathological lesions in the trachea and lungs. Five weeks of post-treatment with Bresol^® (250 and 500 mg/kg, p.o.) showed significant and dose-dependent anti-inflammatory effects against CS-induced lung abnormalities by maintaining the TNF-α and total protein levels within the normal range. Additionally, Bresol^®-treated animals showed normal cyto-architecture of the trachea and lungs. In conclusion, Bresol^® showed dose-dependent protection against CS-induced lung and tracheal injury in rats, which further indicates, Bresol^® is a useful healing agent, may help to decelerate the progression of COPD, and reduce the exacerbations in patients.     

Structural determinants of agonist-induced signaling and regulation of the angiotensin AT1 receptor

Angiotensin II (Ang II) regulates aldosterone secretion by stimulating inositol phosphate production and Ca(2+) signaling in adrenal glomerulosa cells via the G(q)-coupled AT(1) receptor, which is rapidly internalized upon agonist binding. Ang II also binds to the heptahelical AT(2) receptor, which neither activates inositol phosphate signaling nor undergoes receptor internalization. The differential behaviors of the AT(1) and AT(2) receptors were analyzed in chimeric angiotensin receptors created by swapping the second (IL2), the third (IL3) intracellular loops and/or the cytoplasmic tail (CT) between these receptors. When transiently expressed in COS-7 cells, the chimeric receptors showed only minor alterations in their ligand binding properties. Measurements of the internalization kinetics and inositol phosphate responses of chimeric AT(1A) receptors indicated that the CT is required for normal receptor internalization, and IL2 is a determinant of G protein activation. In addition, the amino-terminal portion of IL3 is required for both receptor functions. However, only substitution of IL2 impaired Ang II-induced ERK activation, suggesting that alternative mechanisms are responsible for ERK activation in signaling-deficient mutant AT(1) receptors. Substitution of IL2, IL3, or CT of the AT(1A) receptor into the AT(2) receptor sequence did not endow the latter with the ability to internalize or to mediate inositol phosphate signaling responses. These data suggest that the lack of receptor internalization and inositol phosphate signal generation by the AT(2) receptor is a consequence of its different activation mechanism, rather than the inability of its cytoplasmic domains to couple to intracellular effectors.